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The Renal System

Lecture 1: organization of the renal system


Lecture 2: Reabsorption, secretion and excretion
Lecture 3: control of salt and water balance
Lecture 4: Acid-base balance
Lecture 5: clinical scenarios

Professor Veronica Campbell


Department of Physiology
vacmpbll@tcd.ie

https://medicine.tcd.ie/physiology/student/

Suggested Reading
Sherwood
Principles of Renal Physiology
by Christopher Lote, 4th Edition, Kluwer Academic Publishers

Lecture 1: The renal system

Components of renal system


Structure of nephron
Basic renal functions
Filtration
Assessment of filtration

Functions of kidney
Maintain H2O and salt balance in the body
Maintain proper osmolarity of body fluids, primarily through
regulating H2O balance
Regulate the quantity and concentration of most ECF ions
Maintain proper plasma volume
Help maintain proper acid-base balance in the body
Excreting (eliminating) the end products (wastes) of bodily
metabolism
Excreting many foreign compounds
Producing erythropoietin
Producing renin
Converting vitamin D into its active form

Urinary System
Urine forming organs
Kidneys
Structures that carry urine from the kidneys to the
outside for elimination from the body
Ureters
Urinary bladder
Urethra

Branches of renal artery


Interlobar
Arcuate
Interlobular
Afferent arteriole

Congenital abnormalities
Renal agenesis failure of kidney to develop
1:2500
Unilateral agenesis development of 1 kidney
1:1000
Ectopic kidney abnormal location in pelvis
1:800
Horseshoe kidney - fused

Ureters
Smooth muscle-walled duct
Exits each kidney at the medial border in
close proximity to renal artery and vein
Carry urine to the urinary bladder

Urinary Bladder
Temporarily stores urine
Hollow, distensible, smooth muscle lining
wall
Periodically empties to the outside of the
body through the urethra

Urethra
Conveys urine to the outside of the body
Urethra is straight and short in females
In males
Much longer and follows curving course from
bladder to outside
Dual function
Provides route for eliminating urine from bladder
Passageway for semen from reproductive organs

Kidney

NEPHRON
Functional unit of the kidney
~ 1 million nephrons/kidney
Each nephron has two components
Vascular component
Tubular component

Arrangement of nephrons within kidney gives rise to two


distinct regions
Outer region
Renal cortex

Inner region
Renal medulla

Proximal convoluted
tubule
Glomerulus
Arcuate vein

Efferent arteriole
Afferent arteriole
Distal convoluted tubule

Arcuate artery
Collecting duct
Vasa recta

Descending limb
loop of Henl

Thick ascending limb


of the loop of Henl

Thin ascending limb


of the loop of Henl

Nephron
Two types of nephrons
Distinguished by location and length of
their structures
Juxtamedullary
nephrons (long Loops of Henle; 15%)
Cortical
nephrons (short Loops of Henle)

Nephron
Vascular component
Glomerulus
Ball-like tuft of capillaries
From renal artery, inflowing blood passes through
afferent arterioles which deliver blood to glomerulus
Efferent arteriole transports blood from glomerulus
Efferent arteriole breaks down into peritubular capillaries
which surround tubular part of nephron
Peritubular capillaries join into venules which transport
blood into the renal vein

Water and solutes are filtered through glomerulus


as blood passes through it

Approx 25% C.O


200m

Renal artery
Efferent arteriole

Afferent arteriole

Glomerulus
FILTRATION

PTC

Renal vein

Tubular component
Hollow, fluid-filled tube formed by a
single layer of epithelial cells
Components
1.Bowmans capsule
2. Proximal tubule
3. Loop of Henle
Descending limb
Ascending limb

4. Juxtaglomerular apparatus
5. Distal tubule
6. Collecting duct or tubule

Distal convoluted
tubule
Proximal
convoluted
tubule
- Convoluted apical surface
- sa

Descending
thin limb of
loop of Henl
- Max water permeability

Collecting duct

Basic Renal Processes


Glomerular filtration
Tubular reabsorption
Tubular secretion

Glomerular Filtration
Fluid filtered from the glomerulus into
Bowmans capsule pass through three layers
of the glomerular membrane
Glomerular capillary wall
Single layer of endothelial cells
More permeable to water and solutes than capillaries
elsewhere in the body - highly fenestrated

Basement membrane
Acellular gelatinous layer
Composed of glycoproteins, collagen IV, laminin

Inner layer of Bowmans capsule


Consists of podocytes that encircle the glomerulus tuft

Phagocytosis of macromolecules
4. Mesangial cells phagocytic; contractile and modify SA for filtration

Glomerular Filtration
-The glomerular filtration rate (GFR) is about 125 ml/min in a normal adult
- Ultrafiltrate is cell and protein-free and the concentration of small solutes are
the same as in plasma
- The filtration barrier restricts movement of solutes on a basis of size and
charge.
- Serum albumin has a radius if about 3.5 nm (69kDa) but its negative charge
prevents its movement across basement membrane
- In some diseases the negative charge on the filtration barrier is lost so that
proteins are more readily filtered - a condition called proteinuria

Forces Involved in Glomerular Filtration


Three physical forces
Glomerular capillary
pressure
Plasma-colloid
pressure
Bowmans capsule
pressure

involved
blood
osmotic
hydrostatic

FILTRATION FRACTION
fraction of renal plasma flow that is filtered at the glomerulus

Renal blood flow


1100 ml/min
glomerulus

RPF
600 ml/min

= Glomerular filtration rate


Renal plasma flow
20%

GFR
125 ml/min

Efferent
Arteriole
475 ml/min

tubule

renal
vein

124 ml/min
Urine 1 ml/min

Assessment of GFR using inulin

Vol. plasma inulin cleared/min = vol. plasma filtered/min (GFR)


e.g Inulin clearance rate = 30mg/ml urine x 1.25 ml urine/min
0.30 mg/ml plasma
= 125 ml plasma/min

[U].V
[P]

Clinical note: creatinine clearance used to estimate GFR

Assessment of renal plasma flow with PAH


-para-aminohippuric acid
-Freely filtered and non-reabsorbed
-Any PAH not filtered is secreted from peritubular capillary

PAH clearance = renal plasma flow

[U].V
[P]
600ml/min

Glomerular filtration rate depends on: Net filtration pressure


How much glomerular surface area is available for penetration
How permeable the glomerular membrane is

Glomerular Filtration Rate


Pathologically, plasma-colloid osmotic pressure and
Bowmans capsule hydrostatic pressure can change
Plasma-colloid osmotic pressure
- Dehydrating diarrhea
- Relative increase in colloid pressure in glomerulus
- increase in pressure opposing filtration
GFR

Bowmans capsule hydrostatic pressure


-kidney stone/obstruction of tubule with enlarged prostate
- increase in capsular hydrostatic pressure
- GFR

RENAL BLOOD FLOW (RBF)


Renal blood flow is approx 25% of the cardiac output (1.1 l/min )

- RBF determines GFR


- Renal blood flow is
autoregulated between 90
and 180 mm Hg

Flow l/min
1.5
1.0
0.5
0

Renal blood flow

GFR

0
100
200
Arterial blood pressure, mm Hg

How is GFR maintained at 125ml/min?????

1.
2.

Myogenic response
Tubuloglomerular feedback

RENAL BLOOD FLOW - AUTOREGULATION


Autoregulation uncouples renal function from arterial blood pressure
and ensures that fluid and solute excretion is constant.
1. Myogenic hypothesis
When arterial pressure increases the renal afferent arteriole is stretched
Increase of

Flow

arterial pressure

increases

Vascular smooth muscle contracts to increase resistance


Increase of
vascular tone

Flow
returns to
normal

RENAL BLOOD FLOW - AUTOREGULATION


2. Tubuloglomerular feedback
Alteration of tubular flow is sensed by the macula densa of the
juxtaglomerular apparatus (JGA) and produces a signal that alters
GFR.

Juxtaglomerular
(granular) cells
Efferent
Arteriole

Macula
Densa

Afferent
Arteriole

Distal
tubule

capillaries

Endothelin

Mesangial Cell Contraction


Mesangial cells are modified
smooth muscle cells located on
glomerular capillaries.

Large Surface
Area for Filtration

Filtration
slits

They contract in response


to an increase in MAP
resulting in a decrease in
surface area available for
filtration.
Capillary
lumen

Bowmans
capsule

Relaxation of afferent
arteriole

Bradykinin

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